| Co-Investigator(Kenkyū-buntansha) |
ICHITANI Yukio Tsukuba University, Psycology, Associate Professor, 心理学系, 助教授 (80176289)
IBATA Yasuhiko Kyoto Prefectural University of Medicine, Medicine, Professor, 医学部, 教授 (10079684)
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| Research Abstract |
Although affinity-gels immobilized with typical drugs acting to dopmine receptors did not bind the dopamine receptors because of utilizing the amino- and carboxyl-groups necessitated to bind with dopamine receptors for the immobilization with gel, an another affiniyty-gel immobilized with M-1 compound, which was a derivative from dopamine D2 receptor antagonist, YM 09151-2, and possessed a primary amino-group unnecessitated to binding with dopamine receptors, could bind dopamine receptors in the solubilized fraction from synaptic membrane of bovine striatum. However, it is necessary to reexaminate affinity-elution of bound receptors from affinity-gel because of low purification-fold in obtained purified receptors for the application as antigen into the formation of antibody againsed dopamine receptor. On the other hand, alterations of protein kinase C (PKC) isozymes (alpha, beta, gamma) in the rat striatum follwing the i.p. administration of methamphetamine (MAP), which accelerated the dopamine release from dopaminergic terminals in striatum, were examined using the monoclonal antibodies to clarify the alteration of intracellurar signal-transducing proteins based on the activation of dopamine receptor. Immunohistochemical study revealed that the 4 mg/kg, but not 2 mg/kg, of MAP enhanced the immunoreactivities in striatum. These alterations were dose-and time-dependently detected as the clear appearance of cell bodies of small neurons and agreed with the alterations of stereotyped behavior. Immunoblot analysis showed that the 4 mg/kg of MAP time-dependently enhanced the immunoreactivity against a protein of 80 kDa in the membrane fraction and reduced that in cytosol fraction from striatum. Furthermore, readministration of 2 mg/kg of MAP in the rat follwing the repeated administration of MAP (4 mg/kg, once daily for 14 days) and the withdrawal (8 days) also enhanced the immunoreactivities in striatum and these alterations agreed with the alterations in stereotyped be
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